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Background: A proposed risk factor for cardiovascular disease is high occupational physical activity (OPA), which seems to increase blood pressure (BP), in contrast to leisure time physical activity. Increased BP may lead to hypertension that increase the risk of cardiovascular disease and premature death. Exposures to OPA differ across sex and also within occupational group. Thus, we aimed to investigate associations between OPA and LTPA and BP among men and women using compositional data analysis., Methods: This population-based cross-sectional study, used data from the Copenhagen Aging and Midlife Biobank. OPA and LTPA were self-reported time spent in light physical activity (LPA) during work = standing or walking work; moderate-to-vigorous physical activity (MVPA) during work = heavy manual work; LPA during leisure = light physical activity during leisure; MVPA during leisure = biking or walking as commute to work + daily amount of MVPA during leisure, and sleep. Systolic and diastolic BP (SBP, DBP; mmHg) was measured during sitting rest. We used linear regression models to investigate the association between OPA and LTPA, expressed as isometric log-ratios, and BP. The models were used to predict the BP for reallocated physical activity (PA) compositions (i.e., theoretically 'moving' time from sitting to PA within each domain). Specifically, we predicted the BP for each reallocated PA compositions and calculated the difference in BP between the reallocated compositions and the mean composition., Results: In total, 1,334 women and 2,983 men (mean age 55.1 and 52.5 years, respectively) were included in the analyses. About 50% of the women, and 66% of the men, had hypertension. The linear regressions based on the compositional data analysis, showed no association between OPA and LTPA and SBP among women or men. Among men, less time spent sitting and more time spent in LTPA, compared to the mean composition, was associated with a lower DBP (e.g., 60 min less sitting and 60 min more LTPA: -0.25, 95% CI: -0.05, -0.45 mmHg)., Conclusion: No association between OPA and LTPA and BP was observed across sexes, except between LTPA and DBP among men. This could be due to information bias and lack of precision in self-reported time use data of PA., Trial Registration: None., Competing Interests: Declarations. Ethics approval and consent to participate: The local ethical committee (for the capital region of Denmark) has approved the CAMB as a database combining the three cohorts (No: H-A-2008-126). CAMB has also been registered at the Danish Data Protection Agency as a combined database (No: 2008-41-2938). Competing interests: The authors declare no competing interests. Consent for publication: Not applicable., (© 2024. The Author(s).)

Ongoing monitoring and targeted treatment are important to ensure the best blood-pressure control and thus prevent cardiovascular risks. In this review, we evaluate the findings of four clinical studies investigating the effects of morning versus bedtime dosing of antihypertensives. In three out of four studies, overwhelming results were found favouring bedtime dosing. The same studies have been criticized for mechanistic implausible results and multiple study biases. No harmful effects were reported in relation to bedtime dosing. Thus, antihypertensives can be taken as it is most convenient for the patient., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Background and Aims: The evidence for beta-blocker therapy after myocardial infarction (MI) is randomized trials conducted more than 30 years ago, and the continued efficacy has been questioned., Design and Methods: The ongoing Danish (DANBLOCK) and Norwegian (BETAMI) randomized beta-blocker trials are joined to evaluate the effectiveness and risks of long-term beta-blocker therapy after MI. Patients with normal or mildly reduced left ventricular ejection fraction (LVEF ≥ 40%) will be randomized to open-label treatment with beta-blockers or no such therapy. The event-driven trial will randomize ∼5700 patients and continue until 950 primary endpoints have occurred. As of July 2023, 5228 patients have been randomized. Of the first 4000 patients randomized, median age was 62 years, 79% were men, 48% had a ST-segment elevation myocardial infarction (STEMI), and 84% had a normal LVEF. The primary endpoint is a composite of adjudicated recurrent MI, incident heart failure (HF), coronary revascularization, ischaemic stroke, all-cause mortality, malignant ventricular arrhythmia, or resuscitated cardiac arrest. The primary safety endpoint includes a composite of recurrent MI, HF, all-cause mortality, malignant ventricular arrhythmia, or resuscitated cardiac arrest 30 days after randomization. Secondary endpoints include each of the components of the primary endpoint, patient-reported outcomes, and other clinical outcomes linked to beta-blocker therapy. The primary analysis will be conducted according to the intention-to-treat principle using a Cox proportional hazards regression model. End of follow-up is expected in December 2024., Conclusion: The combined BETAMI-DANBLOCK trial will have the potential to affect current clinical practice for beta-blocker therapy in patients with normal or mildly reduced LVEF after MI., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Our study aimed to examine the effect of testosterone replacement therapy (TRT) on blood pressure in opioid-treated men with relative hypogonadism, and whether the effect of TRT on blood pressure was modified by body composition, red blood cell levels, or carotid intima media thickness. Men (over 18 years old) receiving opioid treatment and total testosterone less than 12 nmol were randomly assigned to receive either TRT or placebo. Baseline and 6-month measurements included anthropometric measurements, office blood pressure (OBPM), 24-h ambulatory blood pressure, blood samples, and carotid ultrasound. The mean systolic OBPM increased by 6.2 mmHg (0.2-12.1) in the TRT group and decreased by 7.0 mmHg (1.0-15.1) in the placebo group, with a mean difference of 13.2 mmHg (3.4-23.1), P  = 0.01. In the TRT group, a 10 mmHg increase in systolic OBPM was associated with an increase in hematocrit of 0.3% points (0.1-0.5) ( P  = 0.01), whereas no association was observed in the placebo group ( P  = 0.266). Daytime SBP showed a nonsignificant increase of 5.2 mmHg (-1.7, 12.1) ( P  = 0.134) in the TRT group compared to that in the placebo group. However, the impact of TRT on the increase in daytime ambulatory blood pressure was significantly accentuated by baseline values of BMI, hematocrit, and hemoglobin. In conclusion, TRT was associated with higher OBPM compared to placebo, and the increase in blood pressure was linked to higher hematocrit during TRT. Our data suggest that men with opioid-induced androgen deficiency, particularly those with obesity or red blood cell levels in the upper normal range, are more susceptible to increased daytime SBP during TRT., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Globally, people living with HIV on antiretroviral therapy have an increased risk of cardiovascular disease. Hypertension is the most important preventable risk factor for cardiovascular disease and is associated with increased morbidity. We conducted an exploratory survey with hypertensive persons living with HIV who received integrated HIV and hypertension care in a large clinic in Uganda between August 2019 and March 2020 to determine factors associated with blood pressure control at six months. Controlled blood pressure was defined as <140/90 mmHg. Multivariable logistic regression was used to determine baseline factors associated with blood pressure control after 6 months of antihypertensive treatment. Of the 1061 participants, 644 (62.6%) were female. The mean age (SD) was 51.1 (9.4) years. Most participants were overweight (n = 411, 38.7%) or obese (n = 276, 25.9%), and 98 (8.9%) had diabetes mellitus. Blood pressure control improved from 14.4% at baseline to 66.1% at 6 months. Comorbid diabetes mellitus (odds ratio (OR) = 0.41, 95% confidence interval (CI) = 0.26-0.64, p < 0.001) and HIV status disclosure (OR = 0.73, 95% CI = 0.55-0.98, p = 0.037) were associated with the absence of controlled blood pressure at 6 months. In conclusion, comorbid diabetes mellitus and the disclosure of an individual's HIV status to a close person were associated with poor blood pressure control among persons living with HIV who had hypertension. Therefore, subpopulations of persons living with HIV with hypertension and comorbid diabetes mellitus may require more thorough assessments and intensive antihypertensive management approaches to achieve blood pressure targets., (© 2022. The Author(s).)

In a randomized controlled trial including 340 people living with obesity, with and without type 2 diabetes, digital coaching has induced significant long-term weight loss compared to the usual methods of care. We investigated whether education level influenced this weight loss and which lifestyle changes supported the digital lifestyle coaching program. The intervention consisted of a 1 h face-to-face motivational interview followed by digital coaching using behavioral change techniques. At 6 months, the weight loss in the intervention group was significantly larger in participants with short education (6.0 vs. 2.2 kg, p < 0.01) ( p = 0.006). Participants with long education experienced initially a modest weight loss, but the effect was maintained, leading to the largest weight loss at 24 months (5.06 [-11.98-1.86] kg), even though there were fewer coaching sessions in the maintenance period. In multiple regression analyses, the greater weight loss in the intervention group was associated with short education ( β = 1.81, p = 0.02), improvements in everyday physical activity ( β = 2.60, p = 0.014) and improvements in dietary habits ( β = 3.84, p = 0.013). In conclusion, at 6 months, the effect of the intervention was more pronounced in people with short education through improvements in everyday physical activity and dietary habits. However, participants with long education sustained their weight loss at 24 months.

Aim: This study aimed to evaluate whether N-terminal pro-brain natriuretic peptide (NT-proBNP) and carotid-to-femoral pulse wave velocity (PWV) carried independent prognostic value in predicting cardiovascular events in apparently healthy individuals beyond traditional risk factors., Methods: A total of 1,872 participants aged 41, 51, 61, or 71 years from the MONItoring of trends and determinants in CArdiovascular disease (MONICA) study were included. Traditional risk factors were assessed, including: smoking status; mean systolic and diastolic blood pressure; body mass index; fasting plasma glucose; serum triglycerides; total, high-density, and low-density lipoprotein cholesterol; NT-proBNP; and PWV. The principal endpoint that was assessed during 16 years of follow-up was a composite of major adverse cardiovascular events (MACE). The secondary endpoints were cardiovascular mortality (CVM), hospitalisation for coronary artery disease (CAD), and a composite of hospitalisation for heart failure (HF) or atrial fibrillation (AF)., Results: At baseline, NT-proBNP was associated with PWV (β=0.14; p<0.001), but not after adjustment for traditional risk factors (β=-0.01; p=0.67). In models including traditional risk factors and PWV, NT-proBNP was associated with all four outcomes (HR MACE =1.33, 95% CI 1.16-1.52; HR CVM =2.02, 95% CI 1.65-2.48; HR CAD =1.29, 95% CI 1.07-1.55; and HR HF or AF =1.79, 95% CI 1.40-2.28). In the same model, PWV was only associated with CVM (HR CVM =1.20, 95% CI 1.01-1.41). No interactions between NT-proBNP and PWV were found. N-terminal pro-brain natriuretic peptide significantly improved net reclassification (NRI) for MACE (NRI=0.12; p=0.03), CVM (NRI=0.33; p<0.001), and HF or AF (NRI=0.33; p<0.001) beyond traditional risk factors, while PWV did not aid in net reclassification improvement for any endpoint., Conclusions: In apparently healthy individuals, NT-proBNP and PWV predicted cardiovascular events independently. N-terminal pro-brain natriuretic peptide improved reclassification for the prediction of MACE, CVM, and hospitalisation for HF or AF beyond traditional risk factors, while PWV did not., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Hypertension, type 2 diabetes, and cardiovascular disease affect the activities of daily living at varying degree. While the effects of aerobic exercise on functional capacity are well-documented, the extent of change for different types of exercise in these chronic conditions remains unexplored. Additionally, there is conflicting evidence regarding the role of exercise in reducing body weight., Methods: We conducted systematic review with meta-analysis and trial sequential analysis and searched various databases from inception to July 2020. We included randomised clinical trials adding any form of trialist defined exercise to usual care versus usual care in people with either hypertension, type 2 diabetes, and/or cardiovascular disease irrespective of setting, publication status, year, and language. The outcomes assessed were i) functional capacity assessed through different scales separately i.e., Maximal Oxygen Uptake (VO 2 max), 6-min walk test (6MWT), 10-m walk test (10MWT), and ii) body weight., Results: We included 950 studies out of which 444 trials randomising 20,098 participants reported on various functional outcomes (355 trials) and body weight (169 trials). The median follow-up was 3 months (Interquartile ranges (IQR): 2.25 to 6). Exercise added to the usual care, improved VO 2 max (Mean Difference (MD):2.72 ml/kg/min; 95% Confidence Interval (CI) 2.38 to 3.06; p < 0.01; I 2  = 96%), 6MWT (MD: 42.5 m; 95%CI 34.95 to 50.06; p < 0.01; I 2  = 96%), and 10MWT (MD: 0.06 m/s; 95%CI 0.03 to 0.10; p < 0.01; I 2  = 93%). Dynamic aerobic and resistance exercise showed a consistent improvement across various functional outcomes, whereas body-mind therapies (MD: 3.23 ml/kg/min; 95%CI 1.97 to 4.49, p < 0.01) seemed especially beneficial for VO 2 max and inspiratory muscle training (MD: 59.32 m; 95%CI 33.84 to 84.80; p < 0.01) for 6MWT. Exercise yielded significant reduction in body weight for people with hypertension (MD: -1.45 kg; 95%CI -2.47 to -0.43; p < 0.01), and type 2 diabetes (MD: -1.53 kg; 95%CI -2.19 to -0.87; p < 0.01) but not for cardiovascular disease with most pronounced for combined exercise (MD: -1.73 kg; 95%CI -3.08 to -0.39; p < 0.05). The very low certainty of evidence warrants cautious interpretations of the results., Conclusion: Exercise seemed to improve functional capacity for people with hypertension, type 2 diabetes, and/or cardiovascular disease but the effectiveness seems to vary with different forms of exercise. The potentially superior improvement in VO 2 max and 6MWT by body-mind therapies and inspiratory muscle training calls for further exploration. Additionally, prescribing exercise for the sole purpose of losing weight may be a potential strategy for people with hypertension and type 2 diabetes. The extent of improvement in functional capacity and body weight reduction differed with different exercise regimens hence personalised exercise prescriptions tailored to individual needs may be of importance. PROSPERO REGISTRATION: PROSPERO registration number: CRD42019142313., (© 2024. The Author(s).)

The VALID BP project was initiated to increase the availability of validated blood pressure measuring devices (BPMDs). The goal is to eliminate non validated BPMDs and minimise over- and underdiagnosis of hypertension caused by inaccurate readings. This study was undertaken to assess the potential return on investment in the VALID BP project. The Framework to Assess the Impact of Translational Health Research was applied to the VALID BP project. This paper focuses on the implementation of the cost benefit analysis aspect of this framework to monetise past research investment and model future research costs, implementation costs, and benefits. Analysis was based on reasoned assumptions about potential impacts from availability and use of validated BPMDs (assuming an end goal of 100% validated BPMDs available in Australia by 2028) and improved skills leading to more accurate BP measurement. After 5 years, with 20% attribution of benefits, there is a potential $1.14-$1.30 return for every dollar spent if the proportion of validated BPMDs and staff trained in proper BP measurement technique increased from 20% to 60%. After eight years (2020-2028) and assuming universal validation and training coverage, the returns would be between $2.70 and $3.20 per dollar spent (not including cost of side effects of unnecessary medication or downstream patient impacts from unmanaged hypertension). This modelled economic analysis indicates there will be positive downstream economic benefits if the availability of validated BPMDs is increased. The findings support ongoing efforts toward a universal regulatory framework for BPMDs and can be considered within more detailed future economic analyses., (© 2023. The Author(s).)

Background: Concomitant type 2 diabetes (T2DM) and cardiovascular disease (CVD) is frequent with a poor prognosis with high risk of comorbidities. Strict risk factor control reduces the risk for complications - yet many people do not achieve treatment targets. The complexity and fragmentation of the healthcare system may, together with the vulnerability of these patients, be a reason., Objective: The purpose of this paper is to describe the protocol of a non-randomized interventional pilot study testing the feasibility and effect of a multidisciplinary, shared care clinic using personalized medicine and coordinated care in people living with concomitant T2D and CVD., Methods: Participants were included from the Holbaek area in Denmark. People suffered from T2DM and CVD and were dysregulated regarding to HbA1c, cholesterol, micro/macroalbuminuaria or blood pressure. Participants went through a thorough evaluation to identify their needs and resources and received consultations every three months for one year., Results: A total of 63 participants with T2DM and CVD were enrolled in the clinic. The participants had a mean age of 69 years and a BMI of 30.9 kg/m 2 . Almost 50 % had heart failure, 95 % dyslipidemia and 91 % hypertension. Around 54 % received GLP-1 agonists and 39 % received SGLT-2-inhibitors., Perspectives: To our knowledge, a similar study with a multidisciplinary, shared care, outpatient clinic treating people living with concomitant T2DM and CVD, has not been performed previously. This study will provide information about the feasibility and efficacy of a multidisciplinary clinic based on changes in cardiovascular risk factors and medication., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction: Exercise is the most recommended lifestyle intervention in managing hypertension, type 2 diabetes, and/or cardiovascular disease; however, evidence in lowering blood pressure is still inconsistent and often underpowered., Method: We conducted a systematic review with meta-analysis and trial sequential analysis of randomized clinical trials adding any form of trialist defined exercise to usual care versus usual care and its effect on systolic blood pressure (SBP) or diastolic blood pressure (DBP) in participants with hypertension, type 2 diabetes, or cardiovascular disease searched in different databases from inception to July 2020. Our methodology was based on PRISMA and Cochrane Risk of Bias-version1. Five independent reviewers extracted data and assessed risk of bias in pairs., Results: Two hundred sixty-nine trials randomizing 15 023 participants reported our predefined outcomes. The majority of exercise reported in the review was dynamic aerobic exercise (61%), dynamic resistance (11%), and combined aerobic and resistance exercise (15%). The trials included participants with hypertension (33%), type 2 diabetes (28%), or cardiovascular disease (37%). Meta-analyses and trial sequential analyses reported that adding exercise to usual care reduced SBP [mean difference (MD) MD: -4.1 mmHg; 95% confidence interval (95% CI) -4.99 to -3.14; P  < 0.01; I2  = 95.3%] and DBP (MD: -2.6 mmHg; 95% CI -3.22 to -2.07, P  < 0.01; I2  = 94%). Test of interaction showed that the reduction of SBP and DBP was almost two times higher among trials from low-and middle-income countries (LMICs) as compared to high-income countries (HICs). The exercise induced SBP reduction was also higher among participants with hypertension and type 2 diabetes compared to participants with cardiovascular disease. The very low certainty of evidence warrants a cautious interpretation of the present results., Conclusion: Adding any type of exercise to usual care may be a potential complementary strategy for optimal management of blood pressure for patients with hypertension, type 2 diabetes, or cardiovascular disease, especially, in LMICs.PROSPERO registration number CRD42019142313., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Metabolic syndrome components may cumulatively increase the risk of diabetic polyneuropathy (DPN) in type 2 diabetes mellitus (T2DM) patients, driven by insulin resistance and hyperinsulinemia. We investigated the prevalence of DPN in three T2DM subgroups based on indices of β-cell function and insulin sensitivity., Research Design and Methods: We estimated β-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) in 4,388 Danish patients with newly diagnosed T2DM. Patients were categorized into subgroups of hyperinsulinemic (high HOMA2-B, low HOMA2-S), classical (low HOMA2-B, low HOMA2-S), and insulinopenic (low HOMA2-B, high HOMA2-S) T2DM. After a median follow-up of 3 years, patients filled the Michigan Neuropathy Screening Instrument questionnaire (MNSIq) to identify DPN (score ≥ 4). We used Poisson regression to calculate adjusted prevalence ratios (PRs) for DPN, and spline models to examine the association with HOMA2-B and HOMA2-S., Results: A total of 3,397 (77%) patients filled in the MNSIq. The prevalence of DPN was 23% among hyperinsulinemic, 16% among classical, and 14% among insulinopenic patients. After adjusting for demographics, diabetes duration and therapy, lifestyle behaviors, and metabolic syndrome components (waist circumference, triglycerides, HDL cholesterol, hypertension, and HbA1c), the PR of DPN was 1.35 (95% CI 1.15-1.57) for the hyperinsulinemic compared with the classical patients. In spline analyses, we observed a linear relation of higher DPN prevalence with increasing HOMA2-B, independent of both metabolic syndrome components and HOMA2-S., Conclusions: Hyperinsulinemia marked by high HOMA2-B is likely an important risk factor for DPN beyond metabolic syndrome components and insulin resistance. This should be considered when developing interventions to prevent DPN., (© 2023 by the American Diabetes Association.)

Purpose: To estimate if newly diagnosed patients with different subphenotypes of type 2 diabetes (T2DM) or latent autoimmune diabetes of adults (LADA) differ with respect to subclinical retinal microvascular structure or diabetic retinopathy (DR)., Methods: This population-based, cross-sectional study of 340 patients (675 eyes) classified patients with recently diagnosed T2DM in different subphenotypes according to beta cell function and insulin sensitivity in to; classical (n = 218), hyperinsulinaemic (n = 86), insulinopenic (n = 20), or LADA (n = 16). Retinal 6-field images were graded according to the International Clinical DR Severity Scale by a retinal expert. Retinal microvascular structures were analysed in eyes by a semiautomatic software., Results: Median age and duration of diabetes were 58.1 (49.9; 65.5) and 0.9 (0.5; 2.4) years, respectively, and 56.8% were male. In a multivariate linear mixed model regression analysis of eyes without DR (n = 570), there was no statistically significant difference in retinal venular or arteriolar width between subtypes and patients with classical T2DM. In addition, eyes from different subphenotypes did not differ according to vessel density, tortuosity or fractal dimension. In a multivariate logistic regression model adjusted for age, sex, HbA1c, diabetes duration, body mass index, mean arterial blood pressure and history of cardiovascular disease, there was a tendency towards persons with hyperinsulinaemic T2DM to be more likely to have DR (OR 1.97, 95% CI 0.95; 4.09) compared to classical T2DM., Conclusion: We found no difference in retinal microvascular structure in patients with newly diagnosed subtypes of T2DM. However, DR may be more prevalent in newly diagnosed patients with hyperinsulinaemic T2DM compared to individuals with classical T2DM., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Objective: To assess the beneficial and harmful effects of adding exercise to usual care for people with hypertension, type 2 diabetes mellitus and/or cardiovascular disease., Design: Systematic review with meta-analysis and trial sequential analysis of randomised clinical trials., Data Sources: The CENTRAL, MEDLINE, EMBASE, Science Citation Index Expanded on Web of Science and BIOSIS searched from inception to July 2020., Eligibility Criteria for Selecting Studies: We included all randomised clinical trials adding any form of trialist defined exercise to usual care versus usual care in participants with either hypertension, type 2 diabetes or cardiovascular disease irrespective of setting, publication status, year and language., Outcome and Measures: The primary outcomes were all-cause mortality, serious adverse events and quality of life., Data Extraction and Synthesis: Five independent reviewers extracted data and assessed risk of bias in pairs. Our methodology was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses, Grading of Recommendations Assessment, Development and Evaluation and Cochrane Risk of Bias-version 1., Results: We included 950 trials, of which 248 trials randomising 21 633 participants reported on our predefined outcomes. All included trials were at high risk of bias. The major types of exercise reported were dynamic aerobic exercise (126/248 trials), dynamic resistance exercise (25/248 trials), and combined aerobic and resistance exercise (58/248 trials). The study participants were included due to cardiovascular diseases (189/248 trials), type 2 diabetes (41/248 trials) or hypertension (16/248 trials). The median intervention period was 3 months (IQR: 2-4 months) and the median follow-up period was 6 months (IQR: 3-8 months) after randomisation. Meta-analyses and trial sequential analyses showed evidence of a beneficial effect of adding exercise to usual care when assessing all-cause mortality (risk ratio (RR) 0.82; 95% CI 0.73 to 0.93; I 2 =0%, moderate certainty of evidence) and serious adverse events (RR 0.79; 95% CI 0.71 to 0.88; I 2 =0%, moderate certainty of evidence). We did not find evidence of a difference between trials from different economic regions, type of participants, type of exercise or duration of follow-up. Quality of life was assessed using several different tools, but the results generally showed that exercise improved quality of life, but the effect sizes were below our predefined minimal important difference., Conclusions: A short duration of any type of exercise seems to reduce the risk of all-cause mortality and serious adverse events in patients with either hypertension, type 2 diabetes or cardiovascular diseases. Exercise seems to have statistically significant effects on quality of life, but the effect sizes seem minimal., Prospero Registration Number: CRD42019142313., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Occupational physical activity (OPA), including occupational lifting (OL), seems to increase the risk of cardiovascular disease (CVD). Knowledge about the association between OL and risk of CVD is sparse, but repeated OL is assumed to result in prolonged raised blood pressure and heart rate (HR) eventually augmenting the risk of CVD. To disentangle parts of the mechanisms behind the raised 24-hour ambulatory blood pressure measurement (24h-ABPM), by exposure to OL, this study aimed to explore the acute differences in 24h-ABPM, relative aerobic workload (RAW) and OPA across workdays with and without OL, and secondary to assess the feasibility and rater agreement of direct field observations of the frequency and load of occupational lifting., Methods: This controlled cross-over study investigates associations between moderate to high OL and 24h-ABPM, RAW in per cent of heart rate reserve (%HRR) and level of OPA. This included 2x24h monitoring of 24h-ABPM (Spacelabs 90217), PA (Axivity) and HR (Actiheart), comprising a workday containing OL and a workday without. The frequency and burden of OL were directly observed in field. The data were time synchronized and processed in the Acti4 software. Differences across workdays with and without OL in 24h-ABPM, RAW and OPA were evaluated using repeated 2 × 2 mixed-models among 60 blue-collar workers in Denmark.. Exposure to OL was estimated by direct manual field observation, registering burden and frequency of OL. Interrater reliability tests were performed across 15 participants representing 7 occupational groups. Interclass correlation coefficient (ICC) estimates of total burden lifted and frequency of lifts were calculated, based on a mean-rating (k = 2), absolute-agreement, 2 way mixed-effects model, indicating the raters as fixed effects., Results: OL led to non-significant increases in ABPM during work-time (systolic Δ1.79 mmHg, 95%CI -4.49-8.08, diastolic Δ0.43 mmHg, 95%CI -0.80-1.65), and on 24-hours basis (systolic Δ1.96 mmHg, 95%CI -3.80-7.72, diastolic Δ0.53 mmHg, 95%CI -3.12-4.18), significant increases in RAW during work (Δ7.74 %HRR, 95%CI 3.57-11.91) as well as a raised level of OPA (Δ4156.88 steps, 95%CI 1898.83-6414.93, Δ-0.67 hours of sitting time, 95%CI -1.25-0.10, Δ-0.52 hours of standing time, 95%CI -1.03-0.01, Δ0.48 hours of walking time, 95%CI 0.18-0.78). ICC estimates were 0.998 (95% CI 0.995-0.999) for total burden lifted and 0.992 (95% CI 0.975-0.997) for frequency of lift., Discussion: OL increased both intensity and volume of OPA among blue-collar workers, which supposedly to contributes to an augmented risk of CVD. Although this study finds hazardous acute effects, further investigations are needed to evaluate the long-term effects of OL on ABPM, HR and volume of OPA, also effects of cumulative exposure to OL would be relevant to investigate., Conclusion: OL significantly raised the intensity and volume of OPA. Direct field observation of occupational lifting showed an excellent interrater reliability., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Background: A key decision in the treatment of atrial fibrillation is choosing between a rhythm control strategy or a rate control strategy as the main strategy. When choosing rate control, the optimal heart rate target is uncertain. The Danish Atrial Fibrillation trial is a randomized, multicenter, two-group, superiority trial comparing strict rate control versus lenient rate control in patients with either persistent or permanent atrial fibrillation at inclusion. To prevent bias arising from selective reporting and data-driven analyses, we developed a predefined description of the statistical analysis., Methods: The primary outcome of this trial is the physical component score of the SF-36 questionnaire. A total of 350 participants will be enrolled based on a minimal important difference of 3 points on the physical component score of the SF-36 questionnaire, a standard deviation of 10 points, a statistical power of 80% (beta of 20%), and an acceptable risk of type I error of 5%. All secondary, exploratory, and echocardiographic outcomes will be hypothesis-generating. The analyses of all outcomes will be based on the intention-to-treat principle. We will analyze continuous outcomes using linear regression adjusting for "site," type of atrial fibrillation at inclusion (persistent/ permanent), left ventricular ejection fraction (≥ 40% or < 40%), and the baseline value of the outcome (all as fixed effects). We define our threshold for statistical significance as a p-value of 0.05 and assessments of clinical significance will be based on the anticipated intervention effects defined in the sample size and power estimations. Thresholds for both statistical and clinical significance will be assessed according to the 5-step procedure proposed by Jakobsen and colleagues., Discussion: This statistical analysis plan will be published prior to enrolment completion and before any data are available and is sought to increase the validity of the DANish Atrial Fibrillation trial., Trial Registration: Clinicaltrials.gov NCT04542785. Registered on Sept 09, 2020., (© 2023. The Author(s).)

A recent study found that only 23.8% of blood pressure (BP) devices available for purchase from Australian pharmacies were validated for accuracy. The extent to which pharmacists are aware of this, and other issues related to the accuracy of BP devices, is not known and gathering this information was the aim of this study. An online survey of Australian pharmacists was distributed via the Pharmaceutical Society of Australia between 1 October and 25 November 2020. Questions were focused on the views of pharmacists related to the accuracy of BP devices. Two hundred and ten pharmacists completed the survey. The accuracy of BP devices sold by pharmacists was considered 'quite' or 'extremely important' to most respondents (94%). However, most respondents (90%) were unaware that less than one-quarter of BP devices sold by Australian pharmacies were validated, and this was 'quite' or 'extremely surprising' to many (69%). Many respondents (64%) associated a particular brand of BP device with greater accuracy. There was low awareness on proper ways to identify accurate BP devices, such as checking reputable online databases (43%). BP devices were stocked in respondents' pharmacies based on perceived quality (50%), accuracy (40%), or as determined by the pharmacy chain (36%). In conclusion, providing accurate BP devices to consumers is important to pharmacists, but they were generally unaware that most devices available from pharmacies were not validated for accuracy. Pharmacist education, alongside advocacy for policies including regulations and strategic action, is required to ensure only validated BP devices are sold in Australia., (© 2022. The Author(s).)

Purpose of Review: There is an increasing need for improved risk stratification to better individualize cardiovascular preventive measures. Although age and sex are strong and easily obtained cardiovascular risk factors (CVRFs), their influence on the prognostic importance of other CVRF, circulating biomarkers and other markers of subclinical cardiovascular damage has not previously been systematically and critically appraised. Therefore, we have revisited the European MORGAM and the Danish MONI10 cohorts., Recent Findings: Theoretically, the relative risk of many CVRF is expected to be lower in older healthy individuals due to a combination of selection bias by disease, higher absolute risk primarily due to older age, and the fact that the CVRF and markers may primarily influence or reflect early parts of the cardiovascular disease process. This influence of age may vary between sexes, as the cardiovascular disease process is delayed and possibly different in women compared with men., Summary: Adjusted for the remaining Systematic COronary Risk Evaluation (SCORE) CVRF, higher SBP, serum cholesterol, soluble urokinase-type plasminogen activator receptor, left ventricular mass index and atherosclerotic plaques were more closely associated with outcomes in individuals younger than 52 years with some sex-specific differences, whereas higher N-terminal pro-brain natriuretic peptide and urine albumin/creatine ratio were more closely associated with outcomes in subjects aged 61 or 71 years., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

This is a case report of an observation of bradycardia and inverted T-waves anteroseptally on the electrocardiogram along with cardiac symptoms, in a previously healthy 35-year-old woman with post-partum pre-eclampsia. Initially, she had no hypertension or proteinuria, which delayed the time of diagnosis. A possible explanation of bradycardia is a baroreceptor-mediated response to hypertension and hypervolaemia. The changes on the electrocardiogram can be explained by pectus excavatum, an enlarged uterus and endothelial dysfunction. One should always consider peri-partum as well as post-partum pre-eclampsia.

Background: Long-term weight loss in people living with obesity can reduce the risk and progression of noncommunicable diseases. Observational studies suggest that digital coaching can lead to long-term weight loss., Objective: We investigated whether an eHealth lifestyle coaching program for people living with obesity with or without type 2 diabetes led to significant, long-term (12-month) weight loss compared to usual care., Methods: In a randomized controlled trial that took place in 50 municipalities in Denmark, 340 people living with obesity with or without type 2 diabetes were enrolled from April 16, 2018, to April 1, 2019, and randomized via an automated computer algorithm to an intervention (n=200) or a control (n=140) group. Patients were recruited via their general practitioners, the Danish diabetes organization, and social media. The digital coaching intervention consisted of an initial 1-hour face-to-face motivational interview followed by digital coaching using behavioral change techniques enabled by individual live monitoring. The primary outcome was change in body weight from baseline to 12 months., Results: Data were assessed for 200 participants, including 127 from the intervention group and 73 from the control group, who completed 12 months of follow-up. After 12 months, mean body weight and BMI were significantly reduced in both groups but significantly more so in the intervention group than the control group (-4.5 kg, 95% CI -5.6 to -3.4 vs -1.5 kg, 95% CI -2.7 to -0.2, respectively; P<.001; and -1.5 kg/m 2 , 95% CI -1.9 to -1.2 vs -0.5 kg/m 2 , 95% CI -0.9 to -0.1, respectively; P<.001). Hemoglobin A 1c was significantly reduced in both the intervention (-6.0 mmol/mol, 95% CI -7.7 to -4.3) and control (-4.9 mmol/mol, 95% CI -7.4 to -2.4) groups, without a significant group difference (all P>.46)., Conclusions: Compared to usual care, digital lifestyle coaching can induce significant weight loss for people living with obesity, both with and without type 2 diabetes, after 12 months., Trial Registration: ClinicalTrials.gov NCT03788915; https://clinicaltrials.gov/ct2/show/NCT03788915., (©Laura Hesseldal, Jeanette Reffstrup Christensen, Thomas Bastholm Olesen, Michael Hecht Olsen, Pernille Ravn Jakobsen, Ditte Hjorth Laursen, Jørgen Trankjær Lauridsen, Jesper Bo Nielsen, Jens Søndergaard, Carl Joakim Brandt. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 23.09.2022.)

Objective: Hyperglycaemia in type 2 diabetes is caused by varying degrees of two defects: low insulin sensitivity and beta-cell dysfunction. We assessed if subgrouping of patients into three pathophysiological phenotypes according to these defects could identify individuals with high or low risk of future cardiovascular events., Design: This is a prospective cohort study., Methods: We assessed estimates of insulin sensitivity and beta-cell function from the homeostasis model assessment-2 in 4209 individuals with recently diagnosed type 2 diabetes enrolled from general practitioners and outpatient clinics in Denmark. Individuals were followed for a composite cardiovascular endpoint (either atherosclerotic outcomes (myocardial infarction, unstable angina pectoris, stroke, coronary or peripheral revascularization), heart failure, or cardiovascular death) and all-cause mortality., Results: Totally 417 individuals with the insulinopenic phenotype (high insulin sensitivity and low beta-cell function) had substantially lower risk of cardiovascular events (5-year cumulative incidence: 4.6% vs 10.1%; age-/sex-adjusted hazard ratio (aHR): 0.49; 95% CI: 0.30-0.82) compared with 2685 individuals with the classical phenotype (low insulin sensitivity and low beta-cell function), driven by atherosclerotic events. Conversely, 1107 individuals with the hyperinsulinaemic phenotype (low insulin sensitivity and high beta-cell function) had more cardiovascular events (5-year cumulative incidence: 12.6%; aHR: 1.33; 95% CI: 1.05-1.69), primarily driven by increased heart failure and cardiovascular death and increased all-cause mortality., Conclusions: Simple phenotyping based on insulin sensitivity and beta-cell function predicts distinct future risks of cardiovascular events and death in patients with type 2 diabetes. These results suggest that precision medicine according to underlying type 2 pathophysiology potentially can reduce diabetes complications.

Background The aim of this study was to prospectively evaluate the effects of renal artery stenting in consecutive patients with severe atherosclerotic renal artery stenosis and high-risk clinical presentations as defined in a national protocol developed in 2015. Methods and Results Since the protocol was initiated, 102 patients have been referred for revascularization according to the following high-risk criteria: severe renal artery stenosis (≥70%) with true resistant hypertension, rapidly declining kidney function, or recurrent heart failure/sudden pulmonary edema. At baseline, the mean 24-hour ambulatory systolic blood pressure was 166.2 mm Hg (95% CI, 162.0-170.4), the defined daily dose of antihypertensive medication was 6.5 (95% CI, 5.8-7.3), and the estimated glomerular filtration rate was 41.1 mL/min per 1.73m 2 (95% CI, 36.6-45.6). In 96 patients with available 3-month follow-up data, mean 24-hour ambulatory systolic blood pressure decreased by 19.6 mm Hg (95% CI, 15.4-23.8; P< 0.001), the defined daily dose of antihypertensive medication was reduced by 52% (95% CI, 41%-62%; P <0.001), and estimated glomerular filtration rate increased by 7.8 mL/min per 1.73m 2 (95% CI, 4.5-11.1; P <0.001). All changes persisted after 24 month follow-up. Among 17 patients with a history of hospitalization for acute decompensated heart failure, 14 patients had no new episodes after successful revascularization. Conclusions In this prospective cohort study, we observed a reduction in blood pressure and antihypertensive medication, an increase in estimated glomerular filtration rate, and a decrease in new hospital admissions attributable to heart failure/sudden pulmonary edema after renal artery stenting. Registration URL: https://clinicaltrials.gov. Identifier: NCT02770066.

Background: Unstable angina (UA) is a component of acute coronary syndrome that is only occasionally included in primary composite endpoints in clinical cardiovascular trials. The aim of this paper is to elucidate the potential benefits and disadvantages of including UA in such contexts., Summary: UA comprises <10% of patients with acute coronary syndromes in contemporary settings. Based on the pathophysiological similarities, it is ideal as a part of a composite endpoint along with myocardial infarction (MI). By adding UA as a component of a primary composite endpoint, the number of events and feasibility of the trial should increase, thus decreasing its size and cost. Furthermore, UA has both economic and quality of life implications on a societal and an individual level. However, there are important challenges associated with the use of UA as an endpoint. With the introduction of high-sensitivity troponins, the number of individuals diagnosed with UA has decreased to rather low levels, with a reciprocal increase in the number of MI. In addition, UA is particularly challenging to define given the subjective assessment of the index symptoms, rendering a high risk of bias. To minimize bias, strict criteria are warranted, and events should be adjudicated by a blinded endpoint adjudication committee., Key Messages: UA should only be chosen as a component of a primary composite endpoint in cardiovascular trials after thoroughly evaluating the pros and cons. If it is chosen to include UA, appropriate precautions should be taken to minimize possible bias., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

[Figure: see text].

Most type 2 diabetes patients are treated in general practice and there is a need of developing and implementing efficient lifestyle interventions. eHealth interventions have shown to be effective in promoting a healthy lifestyle. The purpose of this study was to test the feasibility, including the identification of factors of importance, when offering digital lifestyle coaching to type 2 diabetes patients in general practice. We conducted a qualitative feasibility study with focus group interviews in four general practices. We identified two overall themes and four subthemes: (1) the distribution of roles and lifestyle interventions in general practice (subthemes: external and internal distribution of roles) and (2) the pros and cons for digital lifestyle interventions in general practice (subthemes: access to real life data and change in daily routines). We conclude that for digital lifestyle coaching to be feasible in a general practice setting, it was of great importance that the general practitioners and practice nurses knew the role and content of the intervention. In general, there was a positive attitude in the general practice setting towards referring type 2 diabetes patients to digital lifestyle intervention if it was easy to refer the patients and if easily understandable and accessible feedback was implemented into the electronic health record. It was important that the digital lifestyle intervention was flexible and offered healthcare providers in general practice an opportunity to follow the type 2 diabetes patient closely.

A clinical audit of hospitals in Thailand was conducted to assess compliance with the national hypertension treatment guidelines and determine hypertension control rates across facilities of different sizes. Stratified random sampling was used to select sixteen hospitals of different sizes from four provinces. These included community (<90 beds), large (90-120 beds), and provincial (>120 beds) hospitals. Among new cases, the audit determined whether (i) the recommended baseline laboratory assessment was completed, (ii) the initial choice of medication was appropriate based on the patient's cardiovascular risk, and (iii) patients received medication adjustments when indicated. The hypertension control rates at six months and at the last visit were recorded. Among the 1406 patients, about 75% had their baseline glucose and kidney function assessed. Nearly 30% (n = 425/1406) of patients were indicated for dual therapy but only 43% of them (n = 182/425) received this. During treatment, 28% (198/1406) required adjustments in medication but this was not done. The control of hypertension at six months after treatment initiation was 53% varying between 51% in community and 56% in large hospitals (p < .01). The hypertension control rate at last visit was 64% but varied between 59% in community hospitals and 71% in large hospitals (p < .01). Failure to adjust medication when required was associated with 30% decrease in the odds of hypertension control (OR 0.69, 95% CI 0. 50 to 0.90). Failure to comply with the treatment guidelines regarding adjustment of medication and lost to follow-up are possible target areas to improve hypertension control in Thailand., (© 2020 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Introduction: Atrial fibrillation is the most common heart arrhythmia with a prevalence of approximately 2% in the western world. Atrial fibrillation is associated with an increased risk of death and morbidity. In many patients, a rate control strategy is recommended. The optimal heart rate target is disputed despite the results of the the RAte Control Efficacy in permanent atrial fibrillation: a comparison between lenient vs strict rate control II (RACE II) trial.Our primary objective will be to investigate the effect of lenient rate control strategy (<110 beats per minute (bpm) at rest) compared with strict rate control strategy (<80 bpm at rest) on quality of life in patients with persistent or permanent atrial fibrillation., Methods and Analysis: We plan a two-group, superiority randomised clinical trial. 350 outpatients with persistent or permanent atrial fibrillation will be recruited from four hospitals, across three regions in Denmark. Participants will be randomised 1:1 to a lenient medical rate control strategy (<110 bpm at rest) or a strict medical rate control strategy (<80 bpm at rest). The recruitment phase is planned to be 2 years with 3 years of follow-up. Recruitment is expected to start in January 2021. The primary outcome will be quality of life using the Short Form-36 (SF-36) questionnaire (physical component score). Secondary outcomes will be days alive outside hospital, symptom control using the Atrial Fibrillation Effect on Quality of Life, quality of life using the SF-36 questionnaire (mental component score) and serious adverse events. The primary assessment time point for all outcomes will be 1 year after randomisation., Ethics and Dissemination: Ethics approval was obtained through the ethics committee in Region Zealand. The design and findings will be published in peer-reviewed journals as well as be made available on ClinicalTrials.gov., Trial Registration Number: NCT04542785., Competing Interests: Competing interests: JBF (PI), IR, WB, EEN, FS-H, ODP, UG, CG and JCJ report no competing interests. MHO reports grants from Novo Nordic Foundation outside the submitted work. AB reports personal fees from Bayer, grants from Biotronik, personal fees from Boehringer Ingelheim, personal fees from Bristol-Myers Squibb, personal fees from MSD, grants from Theravance, outside the submitted work. UD reports a research grant from Bayer, personal fees from Pfizer, member of advisory board for Boehringer Ingelheim, member of advisory board for Merck, outside the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Hypertension guidelines recommend that blood pressure (BP) should be measured using a monitor that has passed validation testing for accuracy. BP monitors that have not undergone rigorous validation testing can still be cleared by regulatory authorities for marketing and sale. This is the situation for most BP monitors worldwide. Thus, consumers (patients, health professionals, procurement officers, and general public) may unwittingly purchase BP monitors that are non-validated and more likely to be inaccurate. Without prior knowledge of these issues, it is extremely difficult for consumers to distinguish validated from non-validated BP monitors. For the above reasons, the aim of this paper is to provide consumers guidance on how to check whether a BP monitor has been properly validated for accuracy. The process involves making an online search of listings of BP monitors that have been assessed for validation status. Only those monitors that have been properly validated are recommended for BP measurement. There are numerous different online listings of BP monitors, several are country-specific and two are general (international) listings. Because monitors can be marketed using alternative model names in different countries, if a monitor is not found on one listing, it may be worthwhile cross-checking with a different listing. This information is widely relevant to anyone seeking to purchase a home, clinic, or ambulatory BP monitor, including individual consumers for use personally or policy makers and those procuring monitors for use in healthcare systems, and retailers looking to stock only validated BP monitors., (© 2020 Wiley Periodicals LLC.)

Aims: The 2018 ESC/ESH guidelines for hypertension recommend differential management of patients who are <65, 65-79, and ≥80 years of age. However, it is unclear whether intensive blood pressure lowering is well-tolerated and modifies risk uniformly across the age spectrum., Methods and Results: SPRINT randomized 9361 high-risk adults without diabetes and age ≥50 years with systolic blood pressure 130-180 mmHg to either intensive or standard antihypertensive treatment. The primary efficacy endpoint was the composite of acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. The primary safety endpoint was composite serious adverse events. We assessed whether age modified the efficacy and safety of intensive vs. standard blood pressure lowering using Cox proportional-hazards regression and restricted cubic splines. In all, 3805 (41%), 4390 (47%), and 1166 (12%) were <65, 65-79, and ≥80 years. Mean age was similar between the two study groups (intensive group 67.9 ± 9.4 years vs. standard group 67.9 ± 9.5 years; P = 0.94). Median follow-up was 3.3 years. In multivariable models, age was linearly associated with the risk of stroke (P < 0.001) and non-linearly associated with the risk of primary efficacy events, death from cardiovascular causes, death from any cause, heart failure, and serious adverse events (P < 0.001). The safety and efficacy of intensive blood pressure lowering were not modified by age, whether tested continuously or categorically (P > 0.05)., Conclusion: In SPRINT, the benefits and risks of intensive blood pressure lowering did not differ according to the age categories proposed by the ESC/ESH guidelines for hypertension., Trial Registration: SPRINT (Systolic Blood Pressure Intervention Trial); ClinicalTrials.gov Identifier: NCT01206062, https://clinicaltrials.gov/ct2/show/NCT01206062., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: The World Health Organization recommends consumption of a minimum of 400 g of fruits and vegetables per day for prevention of cardiovascular disease. Low fruit and vegetable intake is associated with an increased risk of stroke by 11% and ischemic heart disease by 31%. The present study aims to explore factors affecting the fruit and vegetable intake in Nepal and its association with history of self-reported major cardiovascular events (myocardial infarction and stroke)., Method: Data for this cross-sectional study were collected as part of the study "Community Based Management of Hypertension in Nepal" initiated in the Lekhnath Municipality in 2013. Demographic and nutrition information were collected using the WHO STEPwise approach to a surveillance tool. Descriptive statistics identified the frequency and percentage of fruit and vegetable intake. A Chi-square test examined the association between fruit and vegetable intake and history of self-reported cardiovascular events, socio-demographic and cardiovascular risk factors. Binary logistic regression analysis identified odds ratio with 95% confidence intervals between fruit and vegetable intake and history of self-reported cardiovascular events., Results: The mean and median intake of fruits and vegetables were 3.3 ± 0.79 and 3 servings respectively. Of the 2815 respondents, 2% (59) reported having a history of major cardiovascular events. The adjusted odds of having a history of major cardiovascular events was 2.22 (95%CI, 1.06-4.66) for those who consumed < 3 servings compared to those who consumed ≥3 servings of fruits and vegetables a day., Conclusion: The respondents who consumed < 3 servings of fruits and vegetables a day had higher odds of a history of major cardiovascular events in comparison to those who consumed ≥3 servings. This finding may carry a policy recommendation for those settings where the current recommendation of having ≥5 servings of fruits and vegetables a day is not possible. Our findings also suggest that surviving a major cardiovascular event was not enough in itself to modify nutritional intake. As many Nepali consumes low amount of fruits and vegetables, appropriate measures should be taken to increase this consumption to prevent cardiovascular morbidity and mortality.

Purpose: To determine the occurrence of physiological significant coronary artery disease (CAD) by coronary CT angiography (CTA) derived fractional flow reserve (FFR CT ) in asymptomatic patients with a new diagnosis (<1 year) of type-2 diabetes mellitus (T2DM)., Methods: FFR CT -analysis was performed from standard acquired coronary CTA data sets. The per-patient minimum distal FFR CT -value (d-FFR CT ) in coronary vessels (diameter ⩾1.8 mm) was registered. The threshold for categorizing FFR CT -analysis as abnormal was a d-FFR CT ⩽0.75. Total plaque volume and volumes of calcified plaque, non-calcified plaque, and low-density non-calcified plaque (LD-NCP) were assessed by quantitative plaque analysis., Results: Overall, 76 patients; age, mean (SD): 56 (11) years; males, n (%): 49(65), were studied. A total of 57% of patients had plaques. The d-FFR CT was ⩽0.75 in 12 (16%) patients. The d-FFR CT , median (IQR), was 0.84 (0.79-0.87). Median (range) d-FFR CT in patients with d-FFR CT ⩽0.75 was 0.70 (0.6-0.74). Patients with d-FFR CT ⩽0.75 versus d-FFR CT >0.75 had numerically higher plaque volumes for all plaques components, although only significant for the LD-NCP component., Conclusion: Every sixth asymptomatic patient with a new diagnosis of T2DM has hemodynamic significant CAD as evaluated by FFR CT. Flow impairment by FFR CT was associated with coronary plaque characteristics.

High blood pressure (BP) is a highly prevalent modifiable cause of cardiovascular disease, stroke, and death. Accurate BP measurement is critical, given that a 5-mmHg measurement error may lead to incorrect hypertension status classification in 84 million individuals worldwide. This position statement summarizes procedures for optimizing observer performance in clinic BP measurement, with special attention given to low-tomiddle- income settings, where resource limitations, heavy workloads, time constraints, and lack of electrical power make measurement more challenging. Many measurement errors can be minimized by appropriate patient preparation and standardized techniques. Validated semi-automated/automated upper arm cuff devices should be used instead of auscultation to simplify measurement and prevent observer error. Task sharing, creating a dedicated measurement workstation, and using semi-automated or solar-charged devices may help. Ensuring observer training, and periodic re-training, is critical. Low-cost, easily accessible certification programs should be considered to facilitate best BP measurement practice., Competing Interests: Conflictos de intereses. R.P. es cofundador de una empresa emergente de medición de la presión arterial, mmHg Inc, que en la actualidad no tiene ningún producto comercializado. N.R.C.C. fue asesor remunerado de la Fundación Novartis (2016–2017) en apoyo de su programa para mejorar el control de la hipertensión en países de ingresos bajos o medianos, lo cual incluyó gastos de viaje para visitar los centros y un contrato para elaborar una encuesta; además, ha prestado asesoramiento consultivo remunerado para Midway Corporation (2017) sobre evaluación exacta de la presión arterial. M.K.R. es vicepresidente de Mejora de Resultados en Salud en la Asociación Médica Estadounidense. G.W. es director de Analítica de Resultados en la Asociación Médica Estadounidense. G.S. preside el Grupo de trabajo de la Sociedad Europea de Hipertensión sobre registro de la presión arterial, es vocal del Comité de Esfigmomanómetros de la ISO, y ha realizado estudios devalidación para diversos fabricantes de tecnologías de medición de la presión arterial y asesorado a los fabricantes sobre desarrollo de aparatos y de programas informáticos. J.K.C. fue el anterior presidente de la Sociedad ARTERY. A.E.S. ha recibido honorarios de Novartis y Omron como ponente por conferencias científicas sobre presión arterial y evaluación de riesgos cardiovasculares, y de Servier por disertar sobre concientizaciónen medición de la presión arterial; además, es asesora remunerada de Abbott Pharmaceuticals sobre medicamentos antihipertensores y presidente de la Sociedad Internacional de Hipertensión. El resto de los autores no revela ningún conflicto de intereses.

Background: Treatment with beta-blockers is currently recommended after myocardial infarction (MI). The evidence relies on trials conducted decades ago before implementation of revascularization and contemporary medical therapy or in trials enrolling patients with heart failure or reduced left ventricular ejection fraction (LVEF ≤ 40%). Accordingly, the impact of beta-blockers on mortality and morbidity following acute MI in patients without reduced LVEF or heart failure is unclear., Methods/design: The Danish trial of beta-blocker treatment after myocardial infarction without reduced ejection fraction (DANBLOCK) is a prospective, randomized, controlled, open-label, non-blinded endpoint clinical trial designed to evaluate the efficacy of beta-blocker treatment in post-MI patients in the absence of reduced LVEF or heart failure. We will randomize 3570 patients will be randomized within 14 days of index MI to beta-blocker or control for a minimum of 2 years. The primary endpoint is a composite of all-cause mortality, recurrent MI, acute decompensated heart failure, unstable angina pectoris, or stroke. The primary composite endpoint will be assessed through locally reported and adjudicated endpoints supplemented by linkage to the Danish national registers. A number of secondary endpoints will be investigated including patient reported outcomes and cardiovascular mortality. Data from similar ongoing trials in Norway and Sweden will be pooled to perform an individual patient data meta-analysis., Discussion: DANBLOCK is a randomized clinical trial investigating the effect of long-term beta-blocker therapy after myocardial infarction in patients without heart failure and reduced LVEF. Results from the trial will add important scientific evidence to inform future clinical guidelines., Trial Registration: Clinicaltrials.gov, NCT03778554. Registered on 19 December 2018. European Clinical Trials Database, 2018-002699-42, registered on 28 September 2018.

Aims: The aim of this study was to examine whether high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and soluble urokinase plasminogen activator receptor (suPAR) carried incremental prognostic value in predicting cardiovascular morbidity and mortality beyond traditional risk factors in apparently healthy individuals., Methods and Results: This was a prospective population-based cohort study comprising 1951 subjects included in the 10-year follow-up of the MONItoring of trends and determinants in CArdiovascular disease (MONICA) study, between 1993 and 1994. The principal endpoint was death from cardiovascular causes. Secondary endpoints were death from any cause, coronary artery disease, heart failure, and cerebrovascular disease. Predictive capabilities of each of the three biomarkers were tested using Cox proportional-hazards regression, Harrell's concordance index (C-index), and net reclassification improvement (NRI). Study participants were aged 41, 51, 61, or 71 years, and equally distributed between the two sexes. During a median follow-up of 18.5 years (interquartile range: 18.1-19.0), 177 (9.1%) subjects died from a cardiovascular cause. Hs-CRP (adjusted standardized hazard ratio (HR): 1.37, 95% confidence interval (CI): 1.17-1.60), NT-proBNP (HR: 1.90, 95% CI: 1.58-2.29), and suPAR (HR: 1.35, 95% CI: 1.17-1.57) were all significantly associated with cardiovascular deaths after adjustment for age, sex, smoking status, systolic blood pressure, and total cholesterol ( p  < 0.001 for all). Furthermore, all three biomarkers were significantly associated with significant NRI. However, only NT-proBNP significantly raised the C-index in predicting death from cardiovascular causes when added to the risk factors (C-index 0.860 versus 0.847; p  = 0.02)., Conclusions: Hs-CRP, suPAR, and particularly NT-proBNP predicted cardiovascular death and may enhance prognostication beyond traditional risk factors in apparently healthy individuals.

High salt (sodium chloride) intake raises blood pressure and increases the risk of developing hypertension, a major risk factor for cardiovascular disease. Little is known about salt intake in Nepal, and no study has estimated salt consumption from 24-hour urinary sodium excretion. Participants (n = 451) were recruited from the Community-Based Management of Non-Communicable Diseases in Nepal (COBIN) cohort in 2018. Salt intake was estimated by analyzing 24-hour urinary sodium excretion. Multivariate linear regression was used to estimate differences in salt intake. The mean (±SD) age and salt intake were 49.6 (±9.8) years and 13.3 (±4.7) g/person/d, respectively. Higher salt intake was significantly associated with male gender (β for female = -2.4; 95% CI: -3.3, -1.4) and younger age (β 10 years  = -1.4; 95% CI: -1.4, -0.5) and higher BMI (β = 0.1; 95% CI: 0.0, 0.2). A significant association was also found between increase in systolic blood pressure and higher salt intake (β = 0.3; 95% CI: 0.0, 0.7). While 55% reported that they consumed just the right amount of salt, 98% were consuming more than the WHO recommended salt amount (<5 g/person/d). Daily salt intake in this population was over twice the limit recommended by the WHO, suggesting a substantial need to reduce salt intake in this population. It also supports the need of global initiatives such as WHO's Global Hearts Initiative SHAKE technical package and Resolves to Save Lives for sodium reduction in low- and middle-income countries like Nepal., (© 2020 Wiley Periodicals, Inc.)

Background: Hypertension, type 2 diabetes mellitus and cardiovascular disease are among the leading causes of mortality globally. Exercise is one of the commonly recommended interventions/preventions for hypertension, type 2 diabetes mellitus and cardiovascular disease. However, the previous reviews have shown conflicting evidence on the effects of exercise. Our objective is to assess the beneficial and harmful effects of adding exercise to usual care for people with hypertension, type 2 diabetes mellitus and/or cardiovascular disease., Methods: This protocol for a systematic review was undertaken using the recommendations of The Cochrane Collaboration, the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) and the eight-step assessment procedure suggested by Jakobsen et al. We plan to include all relevant randomised clinical trials and cluster-randomised trials assessing the effects of adding exercise to usual care for people with hypertension, type 2 diabetes mellitus and/or cardiovascular disease. We will search the Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Latin American and Caribbean Health Sciences Literature (LILACS), Science Citation Index Expanded on Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Science Journal Database (VIP) and BIOSIS. We will systematically assess the risks of random errors using Trial Sequential Analysis as well as risks of bias of all included trials. We will create a 'Summary of Findings' table in which we will present our primary and secondary outcomes, and we will assess the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE)., Discussion: The present systematic review will have the potential to aid patients, clinicians and decision-makers recommending exercise and thereby, benefit patients with hypertension, type 2 diabetes mellitus and/or cardiovascular disease., Systematic Review Registration: PROSPERO CRD42019142313.

Background: Heart failure is a highly prevalent disease with a global prevalence of 37 million, and the prevalence is increasing. Patients with heart failure are at an increased risk of death and morbidity. Traditionally, patients with heart failure have been treated with a beta-blocker in addition to an inhibitor of the renin-angiotensin-aldosterone system. However, new drugs are currently being added to the recommended guideline therapy. The latest drug to be added combines inhibition of the renin-angiotensin-aldosterone system pathway with inhibiting the neprilysin enzyme and is therefore classified as an ARNI. Our objective is to identify the beneficial and harmful effects of ARNIs in the treatment of patient with heart failure., Methods: This protocol for a systematic review was undertaken using the recommendations of the Cochrane, the Preferred Report Items of Systematic reviews with Meta-Analysis Protocols, and the eight-step assessment procedure suggested by Jakobsen and colleagues. We plan to include all relevant randomised clinical trials assessing the use of ARNIs in the treatment of patients with heart failure. We will search the Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Latin American and Caribbean Health Sciences Literature (LILACS), Science Citation Index Expanded on Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Science Journal Database (VIP), and BIOSIS to identify relevant trials. We will also search for grey literature and unpublished trials. Extracted data will be analysed using Review Manager 5, STATA 5, and Trial Sequential Analysis. Our primary outcomes will be all-cause mortality and serious adverse events. We will create a 'Summary of Findings' table in which we will present our primary and secondary outcomes, and we will assess the quality of evidence using the GRADE assessment., Discussion: The present systematic review will have the potential to aid clinicians in decision-making and thereby, benefit patients with heart failure., Systematic Review Registration: PROSPERO CRD42019129336.

Background: The greatest risk factor for cardiovascular disease is hypertension, which can be alleviated via diet, exercise, and adherence to medication. Yet, blood pressure control in Nepal is inadequate, which is partly hindered by a lack of evidence-based, low-cost, scalable, and cost-effective cardiovascular disease prevention programmes. The the community-based management of hypertension in Nepal (COBIN) study was a 12-month community-based hypertension management programme of blood pressure monitoring and lifestyle counselling intervention undertaken by female community health volunteers (FCHVs) in Nepal, against usual care, which showed success in reducing blood pressure. Here we aimed to retrospectively quantify the budget impact and cost-effectiveness of the scale-up of the programme., Methods: In this retrospective analysis, we collected participant-level data from the COBIN study; programme delivery cost data from programme administrators from the COBIN study group; and popualtion and other data from WHO, the World Bank, and the Nepalese Government. We estimated costs per participant and total costs of a national scale-up of the COBIN programme focusing on two scenarios: scenario A, delivery of the intervention to only people aged 25-65 years with hypertension; and scenario B, delivery of the intervention to all adults aged 25-65 years regardless of hypertension status. Effectiveness was based on in-trial blood pressure reductions converted to cardiovascular disease disability-adjusted life-years (DALYs) averted. The primary cost-effectiveness measure was incremental cost per averted cardiovascular disease DALY (calculated using the incremental cost-effectiveness ratio [ICER]) from a health system perspective, including programme delivery and incremental medication costs. We did univariate sensitivity analyses of scenario B to assess the effect of uncertainty in key parameter values in our calculations., Findings: From a health system perspective, the first-year budget impact was US$7·1 million in scenario A and $10·8 million in scenario B. With each subsequent year, the costs decreased by approximately 50%. In the base-case cost-effectiveness analysis, from the health system perspective, scenario A resulted in an ICER of $582 per DALY averted and scenario B resulted in an ICER of $411 per DALY averted. The ICER was most sensitive to uncertainty in the number of total avertable cardiovascular disease DALYs in the eligible population., Interpretation: The programme is projected to be highly cost-effective in both scenarios compared with the WHO thresholds for cost-effectiveness for Nepal. For policy makers intending to meet the UN Sustainable Development Goal of reducing premature mortality from non-communicible diseases, this intervention should be considered., Funding: Duke-NUS Medical School, Singapore., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

: High blood pressure (BP) is a highly prevalent modifiable cause of cardiovascular disease, stroke, and death. Accurate BP measurement is critical, given that a 5-mmHg measurement error may lead to incorrect hypertension status classification in 84 million individuals worldwide. This position statement summarizes procedures for optimizing observer performance in clinic BP measurement, with special attention given to low-to-middle-income settings, where resource limitations, heavy workloads, time constraints, and lack of electrical power make measurement more challenging. Many measurement errors can be minimized by appropriate patient preparation and standardized techniques. Validated semi-automated/automated upper arm cuff devices should be used instead of auscultation to simplify measurement and prevent observer error. Task sharing, creating a dedicated measurement workstation, and using semi-automated or solar-charged devices may help. Ensuring observer training, and periodic re-training, is critical. Low-cost, easily accessible certification programs should be considered to facilitate best BP measurement practice.

Background: It is unclear whether intensive blood pressure management is well-tolerated and affects risk uniformly across the body mass index (BMI) spectrum., Methods: The randomized, controlled Systolic Blood Pressure Intervention Trial (SPRINT) included 9361 individuals ≥50 years of age at high cardiovascular risk, without diabetes mellitus, with systolic blood pressure between 130 and 180 mmHg. Participants were randomized to intensive vs standard antihypertensive treatment and evaluated for the primary composite efficacy endpoint of acute coronary syndromes, stroke, heart failure, or cardiovascular death. The primary safety endpoint was serious adverse events. We used restricted cubic splines to determine the relationship between BMI, response to intensive blood pressure lowering, and clinical outcomes in SPRINT., Results: Body mass index could be calculated for 9284 (99.2%) individuals. Mean BMI was similar between the 2 treatment groups (intensive group 29.9±5.8 kg/m 2 vs standard group 29.8± 5.7 kg/m 2 ; P = 0.39). Median follow-up was 3.3 years (range 0-4.8 years). Body mass index had a significant, J-shaped association with risk of all-cause mortality, stroke, and serious adverse events (P < .05 for all), but these were no longer significant after accounting for key clinical factors (P > .05 for all). Intensive blood pressure lowering reduced the primary efficacy endpoint and increased the primary safety endpoint compared with standard targets, consistently across the BMI spectrum (P interaction > .05)., Conclusion: The overall efficacy and safety of intensive blood pressure lowering did not appear to be modified by baseline BMI among high-risk older adults., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The efficacy and tolerability of intensive blood-pressure lowering may vary by pulse pressure (systolic minus diastolic blood pressure)., Methods: SPRINT randomized 9361 high-risk adults without diabetes and who were ≥50 years with systolic blood pressure 130-180 mm Hg to intensive or standard antihypertensive treatment. The primary efficacy end point was the composite of acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. The primary safety end point was composite serious adverse events. We examined the prognostic implications of baseline pulse pressure and the effects of intensive blood-pressure lowering on clinical outcomes across the spectrum of pulse-pressure values using restricted cubic splines., Results: Mean baseline pulse pressure was similar between the 2 study groups (intensive treatment 61±14 mm Hg vs standard treatment 62±14 mm Hg; P = 0.59). Except stroke, for which the association with pulse pressure was best defined as linear, pulse pressure displayed a nonlinear U-shaped relationship with the risk of all tested clinical end points (P <0.05), though no association remained significant upon multivariable adjustment (P >0.05). The benefit of intensive blood-pressure management on mortality appeared greatest in patients with a pulse pressure ∼60 mm Hg (P = 0.03 for interaction). Pulse pressure did not modify the effect of intensive blood-pressure lowering for other clinical end points (P >0.05 for interaction)., Conclusion: In a large randomized clinical trial of patients with a high risk of cardiovascular events, risks and benefits of intensive blood-pressure lowering did not appear to be modified by baseline pulse pressure. Selection of appropriate candidates for intensive blood-pressure lowering should not be limited by this parameter., (Copyright © 2019 Elsevier Inc. All rights reserved.)